One of the earliest events in viral infections is the binding of a virus to the host cell. Little is presently known concerning the molecular ceptors determine the susceptibility of a host to infection. Myxoviruses, the best understood, have a hemagglutinin that binds cell surface oligosaccharide receptors which contain sialic acid and a neuraminidase that can degrade potential receptors. In view of the fact that various host species contain N- and O-acyl substituted sialic acids which are not common to other species, and that the sialic acids are linked to diverse groups of glycoprotein oligosaccharides, it is important to ascertain whether these variations in structure play a role in the attachment of myxoviruses to target cells. The initial goal of the proposed research will be to systematically determine the specificities of the hemagglutinins and neuraminidases of human, equinine, swine, and avian myxoviruses towards sialyloligosaccharide receptors. Previous attempts to examine the specificity of these proteins have been hampered by the lack of glycoproteins containing a single sialyloligosaccharide of defined sequence. It is now possible to prepare defined sialyloligosaccharides enzymatically by attaching sialic acid to asialoglycoproteins with specific sialytransferases. Asialo-erythrocytes derivatized in this way were used to demonstrate that myxovirus hemagglutinins have strict specificities towards their cell surface receptors (J.C. Paulson, J.E. Sadler, and R.L. Hill (1979) J. Biol. Chem., submitted). The specificities of the hemagglutinin and neuraminidase will initially be determined with defined sialyloligosaccharides carried on soluble or erythrocyte cell surface glycoproteins. These studies will then be extended by testing viral infectivity to cultured cells derivatized to carry single sialyloligosaccharide receptors. Thus, infectivity can be correlated with the specificity of the virus surface glycoproteins. Ultimately, the results obtained can be applied to other types of viruses that bind sialyloligosaccharides like certain oncogenic viruses and the encephalomyocarditis virus.